Objectives:

To perform a comprehensive population genetic study of PARK2. PARK2 mutations are associated with juvenile parkinsonism, Alzheimer disease, cancer, leprosy, and diabetes mellitus, yet ironically, there has been no comprehensive study of PARK2 in control subjects; and to resolve controversial association of PARK2 heterozygous mutations with Parkinson disease (PD) in a well-powered study.

Methods:

We studied 1,686 control subjects (mean age 66.1 ± 13.1 years) and 2,091 patients with PD (mean onset age 58.3 ± 12.1 years). We tested for PARK2 deletions/multiplications/copy number variations (CNV) using semiquantitative PCR and multiplex ligation-dependent probe amplification, and validated the mutations by real-time quantitative PCR. Subjects were tested for point mutations previously. Association with PD was tested as PARK2 main effect, and in combination with known PD risk factors: SNCA, MAPT, APOE, smoking, and coffee intake.

Results:

A total of 0.95% of control subjects and 0.86% of patients carried a heterozygous CNV mutation. CNV mutations found in 16 control subjects were all in exons 1–4, sparing exons that encode functionally critical protein domains. Thirteen patients had 2 CNV mutations, 5 had 1 CNV and 1 point mutation, and 18 had 1 CNV mutation. Mutations found in patients spanned exons 2–9. In whites, having 1 CNV was not associated with increased risk (odds ratio 1.05, p = 0.89) or earlier onset of PD (64.7 ± 8.6 heterozygous vs 58.5 ± 11.8 normal).

Conclusions:

This comprehensive population genetic study in control subjects fills the void for a PARK2 reference dataset. There is no compelling evidence for association of heterozygous PARK2 mutations, by themselves or in combination with known risk factors, with PD.

GLOSSARY

= autosomal recessive juvenile parkinsonism;

= confidence interval;

= copy number variation;

= moving average plots;

= multiplex ligation-dependent probe amplification;

= NeuroGenetics Research Consortium;

= odds ratio;

= Parkinson disease.

Introduction

Transesophageal echocardiography was introduced 4 decades ago. Its use have had very limited clinical indication. Now it has become very useful clinical tool. Indications for its use are almost as indications for transthoracic echocardiography, especially to assess deeper cardiovascular structures. Transesophageal echocardiography is semi-invasive examination with small number of complications.

Aim of the study

To determine usefulness of transesophageal echocardiography in various cardiac conditions based in our experience. Also to encourage use of transesophageal echocardiography as reliable examination.

Methods

All of the patients signed a Term of Free Informed Consent, approved from Ethics Committee. We enrolled 425 patients who have done TEE in last 5 years (2006-2010) by authors. Medical history and Clinical evaluation was carefully performed by expert cardiologists. Procedures were performed in two different centers using machines, PHILIPS iE33 and Siemens accuson CV 70, with equipment attached to a multi frequency 2.5 to 3.5 MHz for TTE and 7.0 MHz for TEE multiplane transducer. TEE were performed and images were obtained according to the standard recommandations.

Results

The results were analyzed by a standard method of descriptive statistics using Pivot Table of Excel Office 2007. Results. We have analyzed 425 transesophageal echocardiography . The examination of the thoracic aorta in severe hypertension patients was conducted in 96 cases; atrial fibrillation in 118; aortic dissection 49 cases, aortic stenosis was evaluated in 28 cases; finding of source of emboli 36 cases; suspicion for aneurysm of the thoracic aorta in 14 cases, 11 cases with suspected endocarditis; the type of intervention for mitral valve was evaluated in 28 cases. Interatrial septum abnormalities 37 cases; and miscellaneous 18 cases. No minor or mayor complications happened.

Conlusion

Transesophageal echocardiography can elucidate many dubious serious conditions immediately after it is performed. So, we think that transesophageal echocardiography is very useful tool in everyday clinical use, almost without complications if it is done correctly.

Aims: To prospectively assess the WHO clinical decision rule (CDR) for group A beta haemolytic streptococcal (GABHS) pharyngitis in three countries.

Methods: A prospective, observational cohort study in urban outpatient clinics in Rio de Janeiro, Cairo, and Zagreb. There were 2225 children aged 2–12 years with cough, rhinorrhoea, red or sore throat; 1810 of these with sore throat were included in the analysis.

Results: The proportion of children presenting with sore throat and found to have GABHS pharyngitis ranged from 24.6% (Brazil) to 42.0% (Croatia). WHO CDR sensitivity was low for all sites in both age groups. In children age 5 or older, sensitivity ranged from 3.8% in Egypt to 10.8% in Brazil. In children under 5, sensitivity was low (0.0–4.6%) Specificity was high in both age groups in all countries (93.8–97.4%).

Conclusions: In these populations, the current WHO CDR has high specificity, but low sensitivity; it did not detect up to 96.0% of children who have laboratory confirmed GABHS pharyngitis. A CDR with higher sensitivity should be developed for use in regions where rheumatic fever and rheumatic heart disease are still major health problems.